MONOCLONAL-ANTIBODY ALPHA-IR-3 INHIBITS NONSMALL CELL LUNG-CANCER GROWTH IN-VITRO AND IN-VIVO

The ability of monoclonal antibody (mAb) alpha IR-3 to interact with n on-small cell lung cancer (NSCLC) cells was investigated. MAb alpha IR -3 inhibited specific binding of I-125-IGF-I and I-125-alpha-IR-3 to a panel of 8 NSCLC cell lines with high affinity (IC50 = 200 and 50 ng/ ml, respectively). I-125-alpha IR-3 bound with high affinity (Kd = 40 ng/ml) to a single class of sites (Bmax = 8,000/cell) using NCI-H838 c ells. I-125-alpha IR-3 was internalized when exposed to NCI-H838 or H1 299 cells at 37 degrees C but not 4 degrees C. alpha IR-3 immunoprecip itated major 90 and 130 kD proteins. IGF-I stimulated and alpha IR-3 i nhibited the clonal growth of NCI-H1299 cells. alpha IR-3 slowed the g rowth of NCI-H157 and H838 xenografts in nude mice. In a biodistributi on study I-125-alpha IR-3 was preferentially localized to the tumor as opposed to other organs. These data suggest that IGF-I may be a regul atory agent in NSCLC. (C) 1996 Wiley-Liss, Inc.